Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitogenic and adjuvant effect in vitro of MER (methanol extracted residue of tubercle bacilli), on Balb/C and nu/nu immunocompetent cells was examined and compared with the effect of PPD, LPS, DS, PHA and ConA. MER activated DNA synthesis in spleen cells of Balb/C and nu/nu mice and in blood cultures of Balb/C. The stimulation of DNA synthesis by MER in spleen cells was not macrophage dependent. Bone marrow and 1ymph node cells were slightly stimulated while thymus cells were not affected. Both MER and PPD enhanced the in vitro immune response of Balb/C mice to SRBC and to TNP (trinitrophenyl) hapten. MER, LPS and PPD enhanced the immune response of nude spleen cells to SRBC in vitro.
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PMID:Mitogenic and adjuvant activity of a methanol extraction residue (MER) of tubercle bacilli on mouse lymphoid cells in vitro. 77 Mar 12

New Zealand Black (NZB) mice spontaneously develop an autoimmune syndrome similar to that of systemic lupus erythematosus. Numerous abnormalities in T lymphocyte development have been reported in NZB mice, and the autoimmune syndrome can be adoptively transferred to naive recipients using bone marrow cells. In the present study, we have used an adoptive transfer system to study quantitatively the relative prothymocyte activity of marrow in either young (4-6 weeks of age) or older (8-10 months of age) NZB mice. Our results demonstrate that NZB marrow has approximately 7-fold more prothymocyte activity than that of marrow in SEA mice, a histocompatible, non-autoimmune prone normal strain of mice. This was ascertained by a competitive repopulation assay, in which mixtures of NZB and SEA prothymocytes were compared directly for their ability to repopulate the thymus of adoptive recipients. This increase in prothymocyte activity in the primary recipient of NZB marrow was associated with an increased competitive advantage of NZB marrow prothymocytes over that of SEA marrow prothymocytes in repopulating the hemopoietic (bone marrow) compartment of the primary host. These findings suggest that elevated prothymocyte activity in NZB mice, along with our previously presented evidence for abnormalities of thymocytopoiesis in NZB mice, may be important in their predisposition for autoimmunity.
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PMID:Evidence for elevated prothymocyte activity in the bone marrow of New Zealand Black (NZB) mice. Elevated prothymocyte activity in NZB mice. 158 12

The Patch (Ph) mutation in mice is a deletion of the gene encoding the platelet-derived growth factor receptor alpha subunit (PDGFR alpha). Patch is a recessive lethal recognized in heterozygotes by its effect on the pattern of neural crest-derived pigment cells, and in homozygous mutant embryos by visible defects in craniofacial structures. Since both pigment cells and craniofacial structures are derived from the neural crest, we have examined the differentiation of other crest cell-derived structures in Ph/Ph mutants to assess which crest cell populations are adversely affected by this mutation. Defects were found in many structures populated by non-neuronal derivatives of cranial crest cells including the thymus, the outflow tract of the heart, cornea, and teeth. In contrast, crest-derived neurons in both the head and trunk appeared normal. The expression pattern of PDGFR alpha mRNA was determined in normal embryos and was compared with the defects present in Ph/Ph embryos. PDGFR alpha mRNA was expressed at high levels in the non-neuronal derivatives of the cranial neural crest but was not detected in the crest cell neuronal derivatives. These results suggest that functional PDGF alpha is required for the normal development of many non-neuronal crest-derived structures but not for the development of crest-derived neuronal structures. Abnormal development of the non-neuronal crest cells in Ph/Ph embryos was also correlated with an increase in the diameter of the proteoglycan-containing granules within the crest cell migratory spaces. This change in matrix structure was observed both before and after crest cells had entered these spaces. Taken together, these observations suggest that functional PDGFR alpha can affect crest development both directly, by acting as a cell growth and/or survival stimulus for populations of non-neurogenic crest cells, and indirectly, by affecting the structure of the matrix environment through which such cells move.
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PMID:A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. 163 76

Age-related changes manifested in MHC-linked recognition of bone marrow (BM) cells by the thymic stroma were studied in vitro model of thymus-BM chimeras. Fetal thymuses (FT) depleted of self-lymphocytes were colonized with BM cells from syngeneic and allogeneic donor mice. When cells from young (3-month-old) or old (24-month-old) donors syngeneic to the stroma were seeded in a mixture with cells of allogeneic young origins (C57BL/6J-Thy1.2 and ARK/J-Thy1.1 seeded onto C57BL/6J FT), the syngeneic cells showed an age-related developmental advantage. Accordingly, cells from the old syngeneic mice manifested a significantly reduced capacity to compete with allogeneic cells when compared with the young syngeneic cells. When allogeneic BM cells from young or old mice were seeded onto the thymic stroma in a mixture with BM cells from young donors syngeneic to that stroma (BALB/c-Thy1.2 mixed with C57BL/Ka-Thy1.1 seeded onto C57BL/6J or C57BL/Ka FT), the Thy1+ cells which developed were mainly of syngeneic origin. The age of the allogeneic cells had no significant effect on the results. However, when old allogeneic cells were mixed with old syngeneic cells, the developmental advantage of the syngeneic cells was not manifested. When seeding of allogeneic cells was followed 1 day later by seeding of syngeneic cells, the syngeneic advantage was eliminated, suggesting that the MHC-linked competition began during the first 24 hr of contact with the thymic tissue. When BM-derived thmocytes grown in FT explants were transferred onto second FT recipient explants of the same genotype as the first ones, the syngeneic advantage was abolished, suggesting either that the thymic microenvironment was modified as a result of colonization or that it induced a change in the BM cells. In this respect, the young allogeneic BM-derived thymocytes showed a significant advantage when compared with the old cells. Thus, the MHC-linked syngeneic preference in the early development of BM cells is also manifested in aging mice, yet at a level that is significantly reduced compared with that seen in the young mice.
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PMID:Interactions of bone marrow cells from young and old mice with syngeneic and allogeneic thymic tissue. 193 73

There is now convincing evidence for the imposition of self tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we and other investigators have used transgenic technology to direct expression of a known "nonself" gene to a given extrathymic tissue. No lymphocytic infiltration was ever seen in transgene-expressing tissues, even if the mice were given normal syngeneic (nontransgenic) spleen cells intravenously or were stimulated with H-2Kb spleen cells. Infiltration did, however, occur in irradiated transgenic recipients of H-2Kb immune spleen cells. In MET-Kb mice, this infiltrate diminished with time, raising the possibility that peripheral tolerance may even have been induced in immune cells. H-2Kb-bearing skin was accepted in young RIP-Kb mice but rejected in older mice, which had lost more than 75% of their beta cells as a result of the overexpression of H-2Kb. This loss of tolerance thus occurred when the concentration of the tolerogen, H-2Kb, fell below some critical threshold. Following in vitro stimulation, spleen cells from young RIP-Kb mice could not kill H-2Kb-bearing targets, but could respond to third party targets. Thymus cells, on the other hand, could be stimulated to kill both targets, clearly indicating that tolerance was not imposed intrathymically. Spleen cells from older RIP-Kb mice (those that had lost most of their beta cells) killed both targets, which is in agreement with the in vivo data. Reactivity to H-2Kb was restored to young spleen cells by providing them with IL-2. Two hypotheses were proposed to account for the above findings: tolerance results either from the deletion or functional silencing of high-affinity effector cells or of regulatory, IL-2-producing helper T cells. As it is difficult to distinguish between these, we have produced a second series of transgenic mice (F3+) with rearranged TCR genes encoding an anti-H-2Kb TCR and derived "double-transgenic" (F3+RIP+) offspring by mating these mice with RIP-Kb mice. The transgenic TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. There were in the thymus very few CD4+ and very few CD4+8+ cells in both F3+ and F3+RIP+ mice and, in the double-transgenic mice, there was no evidence of deletion of CD8+V beta 11+ cells in the periphery although they showed tolerance to H-2Kb-bearing skin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A transgenic approach to the study of peripheral T-cell tolerance. 193 38

Monoclonal antibodies (mAbs) BW 625 and BW 704, of the IgG3 isotype, bound to immunochemically indistinguishable epitopes on ganglioside II3(Neu-Ac)2-GgOse3-Cer. Despite this fact the mAbs showed a differential binding pattern on human glioma cell lines i.e. immunohistochemical data indicate that the detected epitopes are not identical. Furthermore, either mAb is able to mediate the antibody-dependent cellular cytotoxicity reaction (ADCC) and the human-complement-dependent cytotoxicity reaction (CDC) with epitope-expressing tumor cells. All cryopreserved tissue specimens from gliomas and neuroblastomas were immunohistochemically stained, whereas the other small round cell tumors of childhood, as well as melanomas and small-cell lung carcinomas, were essentially negative. Positive staining of normal cryopreserved tissues was restricted to amyelinic axons, Hassal's bodies and some connective tissue fibers in thymus and the tegumentary epithelium of skin. The high selectivity of mAb BW 704 for gliomas and neuroblastomas, the lack of cross-reactivity with major tissues and the strong ADCC and CDC potential argue for the use of mAb BW 704 in immunotherapy of neuroblastomas and gliomas.
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PMID:Monoclonal antibodies against epitopes on ganglioside GD2 and its lactones. Markers for gliomas and neuroblastomas. 247 92

A DNA-binding protein from human placenta, methylated DNA-binding protein (MDBP), binds to certain DNA sequences only when they contain 5-methylcytosine (m5C) residues at specific positions. We found a very similar DNA-binding activity in nuclear extracts of rat tissues, calf thymus, human embryonal carcinoma cells, HeLa cells, and mouse LTK cells. Like human placental MDBP, the analogous DNA-binding proteins from the above mammalian cell lines formed a number of different low-electrophoretic-mobility complexes with a 14-bp MDBP-specific oligonucleotide duplex. All of these complexes exhibited the same DNA methylation specificity and DNA sequence specificity. From the extracts of rat and calf tissues, oligonucleotide protein complexes formed that also had the same specificity as human placental MDBP although they had a higher electrophoretic mobility probably due to digestion by proteases in the nuclear extracts. Although MDBP activity was found in various mammalian cell types, it was not detected in extracts of cultured mosquito cells and so may be associated only with cells with vertebrate-type DNA methylation.
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PMID:Methylated DNA-binding protein is present in various mammalian cell types. 290 11

The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.
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PMID:Activation of T lymphocytes results in an increase in H-2-encoded neuraminidase. 387 51

The presence of specific binding of SEA with membranes of lymphocytes from rabbit thymus is established. Components of a glycolipid nature are absent in the composition of the receptor complex for SEA on T-lymphocytes. Suitable conditions for the solubilization of the receptor membrane fraction by Triton X-100 are described. The SEA-binding membrane fraction is isolated by means of an affinity-chromatography method. The main component of the fraction is a protein with molecular mass 42 kd. The isolated protein inhibits the specific binding of [125I] SEA on cell (T-lymphocytes) and subcell (membrane) levels.
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PMID:Membrane protein from rabbit T-lymphocytes, specifically binding staphylococcal enterotoxin A (SEA). 387 54

The binding characteristics of 125I-labelled staphylococcal enterotoxin A (125I-SEA), a T-cell mitogen, to murine lymphoid cell subpopulations were analyzed. Both T- and B-lymphocytes from murine spleens possess specific binding sites for SEA, as do T-lymphocytes from thymus. B-lymphocytes appear to have a greater capacity for binding of 125-SEA than do T-lymphocytes from either thymus or spleen. Enterotoxin did not specifically bind to thioglycollate-induced peritoneal exudate cells (PECs), used as a source of macrophages. Adherent PECs however, incorporated 125-ISEA by fluid phase endocytosis. When exposed to SEA and thoroughly washed, macrophages stimulate lymphocyte mitogenesis in spleen or thymus cell cultures not directly exposed to toxin. Maximum mitogenic stimulation took place only when both PECs and lymphocytes were exposed to SEA. The presence of splenic B-lymphocytes enhanced the mitogenic response of thymus derived T-cells to SEA. Thus, B-lymphocytes appear to contribute to SEA mitogenesis. These data suggest that mitogenic stimulation and possibly other immunological phenomena associated with SEA occur as a result of complex interactions between cellular components of the immune system.
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PMID:Staphylococcal enterotoxin induced mitogenesis: toxin binding and cell-cell interactions. 660 72


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